To the best of our knowledge, there is no published randomized control trial (RCT) of alcohol on levels of urinary estrogen metabolites (including the catechol estrogens) and androgens in postmenopausal women. Studies, which used questionnaires to assess alcohol intake, report inconsistent associations with sex hormone levels in women. Thus, the mechanisms by which alcohol consumption affect breast cancer risk remains unclear because of the lack of RCTs. We will capitalize on the availability of stored urine samples from the "Women's Alcohol Study (WAS)," a RCT using a cross-over design conducted at the USDA'S Beltsville Human Nutrition Research Center, MD. Urine samples (n=387) were collected at baseline, week 4 and week 8 of the trial from 53 non-smoking postmenopausal women not on hormone replacement therapy (HRT) who completed the trial. Our hypothesis is that low to moderate (Og/d, 15g/d, 30g/d) alcohol consumption for 4 and 8 weeks will increase levels of urinary estrogens, which will positively correlate with markers of oxidative stress, IGF1 and IGFBP3, thereby providing a mechanistic explanation for the alcohol breast cancer association seen in epidemiologic studies. In animal experiments oxidative stress has been shown to play a crucial role in estrogen-induced carcinogenesis. There is also suggestive evidence for a synergistic effect between IGFs and estrogens on breast cancer risk. We further hypothesize that alcohol and estrogen metabolizing gene single-nucleotide polymorphism (SNP) variant alleles may modify the levels of urinary estrogens in our study population. The proposed experimental study has the potential to fill crucial gaps in knowledge on how dose and duration of alcohol consumption affect urinary estrogen metabolites in postmenopausal women. In addition, if alcohol-induced changes in urinary estrogens correlate with levels of oxidative stress, it would support the findings from animal experiments that estrogens cause cancer when cells also experience oxidative stress. The implications of this research include translation of the findings into prevention messages aimed at modifying alcohol intake to avert risk of breast cancer. Because behavior modification may be difficult to achieve, alternatively, our findings may form the basis to propose studies aimed at targeting oxidative stress and the IGF pathway to offset some of the risk associated with alcohol consumption. [unreadable] [unreadable] [unreadable]